Obsessive-compulsive disorder (OCD) is a severe, heritable condition with a lifetime prevalence of about two percent of the population. The mode of inheritance is poorly understood but is likely complex, involving multiple loci of small to moderate effect. Our laboratory has been active in studies of OCD and of its genetics for over 10 years, and in 2001 became one of the founding sites of a multi-center genetic study of OCD (P.I.: Dr. Gerald Nestadt of Johns Hopkins University.) This study was approved via a competitive NIMH extramural grant application. Due to the accumulation of evidence supportive of genetic contributions to OCD, a series of association and linkage studies of candidate genes has been undertaken and reported in the literature, but only one, very small genome- wide scan of OCD has been reported. Our OCD genetic studies in the NIMH IRP contribute DNA and family evaluation data to this national multi-site, genome-wide study of OCD which recently submitted DNA and phenotypic information to CIDR for a 10cM genome scan (Samuels et al., in press). Gene and interview data will be shared within this consortium of investigators studying OCD and will eventually be shared with the scientific community following NIMH guidelines. In addition, within the NIMH-IRP, exploratory analyses of DNA, clinical features and personality characteristics of OCD probands and of disorders related to OCD are being used to assess the candidacy status of gene variants and to better define the familial OCD phenotype. In one such study, factor and cluster analysis of 70 OCD symptoms rated in each of the 317 patients with OCD revealed a four factor grouping of symptoms which showed specific relationships to comorbid psychiatric disorders (Hasler et al., 2005). Thus, Factor I (aggressive, sexual, religious and somatic obsessions, and checking compulsions) was broadly associated with comorbid anxiety disorders and depression; Factor II (obsessions of symmetry, and repeating, counting and ordering/arranging compulsions) with bipolar disorders and panic disorder/agoraphobia; and Factor III (contamination obsessions and cleaning compulsions) with eating disorders. Factors I and II were associated with early onset OCD. The frequent co-occurrence of OCD with other psychiatric disorders and the relatively specific association patterns between OCD symptom dimensions and comorbid disorders support the importance of OCD subtyping for genetic, treatment, and other research studies of this heterogeneous disorder.